Contributions to Science

Identification of transcriptional adaptors/coactivators Gcn5/Ada2/Ada3 and discovery of novel histone modifications and mechanisms in transcription. We discovered the first transcriptional adaptors, which we showed associate with DNA binding activators. This was groundbreaking as a new model for transcriptional activation, and set the stage for understanding how histone enzymatic modifiers are recruited to genes. Our work was the first to reveal the importance of adaptor Gcn5 acetylation activity in transcriptional activation, and helped to unify understanding of transcription and chromatin regulation. We discovered numerous novel histone modifications, histone modification cross-talk, and sequential histone modifications in transcription, including histone phosphorylation/acetylation, ubiquitylation/deubiquitylation.

Discovery of tumor suppressor p53 post-translational modifications and their mechanisms including activating p53 acetylation, repressive p53 methylation, and novel chromatin pathways in p53-mediated transcriptional activation. Our work revealed new enzyme modifiers of p53, including acetylation and methylation, and their functions in regulating p53 activity. In particular, we discovered that p53 methylation is generally repressive to its function. These findings spurred broad efforts in discovery of transcription factor modifications. Recently, we discovered novel pathways used by wild type and mutant p53 in regulating chromatin structure/function.

Discovery of chromatin mechanisms controlling gametogenesis in yeast and mammals. We have investigated chromatin mechanisms governing the profound restructuring and compaction of chromatin during gametogenesis (sporulation in yeast and spermatogenesis in mammals). Our work has revealed novel mechanisms and chromatin enzymes, and has showed that certain chromatin changes are conserved from yeast to mouse.